Conjunctival papillary formation and
corneal damage, which are seen in severe types of allergic
conjunctival diseases, are mediated by eosinophils. Eosinophils themselves are not able to recognize a specific
antigen (Ag) and thus, Ag-specific T cells are thought to be important for eosinophilic infiltration into the conjunctiva.
Cytokines, which are produced by Ag-specific T cells followed by Ag recognition, are considered to be involved in eosinophilic infiltration. Therefore, we investigated the involvement of
cytokines, which are produced by immunocompetent cells and conjunctival cells, in the infiltration of inflammatory cells into the conjunctiva, using an animal model for allergic
conjunctival diseases (experimental immune-mediated blepharoconjunctivitis, EC). The peak of expression of Th 2
cytokines such as
interleukin (IL)-4 in the rat conjunctiva was 6 and 12 hours after Ag challenge. In contrast, expression of Th1
cytokines such as
interferon (IFN)-gamma persisted up to 48 hours after Ag challenge. The kinetic change of
IL-4 was concordant with eosinophilic infiltration into the conjunctiva and that of IFN-gamma was in accord with infiltration of macrophages. To investigate the roles of these
cytokines, we induced
conjunctivitis in
cytokine knockout mice. The infiltration of inflammatory cells was attenuated in
IL-4 knockout mice, whereas it was augmented in IFN-gamma knockout mice. To further elucidate the roles of these
cytokines, we induced and analyzed EC in Brown Norway rats. Eosinophilic infiltration was increased in EC induced by the transfer of T cells, which were stimulated by
IL-4. In addition, systemic treatment with IFN-gamma inhibited eosinophilic infiltration in EC induced by active immunization, but did not affect infiltration of inflammatory cells in EC induced by passive immunization. These results demonstrate that
IL-4 and IFN-gamma are involved in the infiltration of eosinophils and macrophages, respectively. In addition, IFN-gamma exerts its suppressive effects on the development of EC only during the induction phase of EC. Further detailed studies investigating the roles of
cytokines in the conjunctiva will elucidate the developing mechanism of allergic
conjunctival diseases. These studies will provide important clues for a therapeutic approach in targeting
cytokines.